More Like this

1. Copper( ii ) ketimides in sp 3 C–H amination

   https://doi.org/10.1039/D1SC01990B  

   Jayasooriya, Isuri U. ; Bakhoda, Abolghasem ; Palmer, Rachel ; Ng, Kristi ; Khachemoune, Nour L. ; Bertke, Jeffery A. ; Warren, Timothy H. ( December 2021 , Chemical Science)

   Commercially available benzophenone imine (HNCPh 2 ) reacts with β-diketiminato copper( ii ) tert -butoxide complexes [Cu II ]–O t Bu to form isolable copper( ii ) ketimides [Cu II ]–NCPh 2 . Structural characterization of the three coordinate copper( ii ) ketimide [Me 3 NN]Cu–NCPh 2 reveals a short Cu-N ketimide distance (1.700(2) Å) with a nearly linear Cu–N–C linkage (178.9(2)°). Copper( ii ) ketimides [Cu II ]–NCPh 2 readily capture alkyl radicals R˙ (PhCH(˙)Me and Cy˙) to form the corresponding R–NCPh 2 products in a process that competes with N–N coupling of copper( ii ) ketimides [Cu II ]–NCPh 2 to form the azine Ph 2 CN–NCPh 2 . Copper( ii ) ketimides [Cu II ]–NCAr 2 serve as intermediates in catalytic sp 3 C–H amination of substrates R–H with ketimines HNCAr 2 and t BuOO t Bu as oxidant to form N -alkyl ketimines R–NCAr 2 . This protocol enables the use of unactivated sp 3 C–H bonds to give R–NCAr 2 products easily converted to primary amines R–NH 2 via simple acidic deprotection. 

   more » « less
2. Remote C–H Functionalization via Selective Hydrogen Atom Transfer

   https://doi.org/10.1055/s-0036-1591930  

   Stateman, Leah ; Nakafuku, Kohki ; Nagib, David ( April 2018 , Synthesis)

   The selective functionalization of remote C–H bonds via intramolecular hydrogen atom transfer (HAT) is transformative for organic synthesis. This radical-mediated strategy provides access to novel reactivity that is complementary to closed-shell pathways. As modern methods for mild generation of radicals are continually developed, inherent selectivity paradigms of HAT mechanisms offer unparalleled opportunities for developing new strategies for C–H functionalization. This review outlines the history, recent advances, and mechanistic underpinnings of intramolecular HAT as a guide to addressing ongoing challenges in this arena. 1 Introduction 2 Nitrogen-Centered Radicals 2.1 sp3 N-Radical Initiation 2.2 sp2 N-Radical Initiation 3 Oxygen-Centered Radicals 3.1 Carbonyl Diradical Initiation 3.2 Alkoxy Radical Initiation 3.3 Non-alkoxy Radical Initiation 4 Carbon-Centered Radicals 4.1 sp2 C-Radical Initiation 4.2 sp3 C-Radical Initiation 5 Conclusion 

   more » « less
3. Copper Catalyzed sp3 C-H a-Acetylation

   https://doi.org/10.26434/chemrxiv.11407116  

   Okoromoba, O ; Jang, E.S. ; McMullin, C. ; Cundari, T. R. ; Warren, T. H. ( December 2019 , ChemRxiv)

   null (Ed.)

   α-substituted ketones are important chemical targets as synthetic intermediates as well as functionalities in in natural products and pharmaceuticals. We report the sp3 C-H α-acetylation of sp3 C-H substrates R-H with arylmethyl ketones ArC(O)Me to provide α-alkylated ketones ArC(O)CH2R at RT with tBuOOtBu as oxidant via copper(I) β-diketiminato catalysts. Proceeding via alkyl radicals R•, this method enables α-substitution with bulky substituents without competing elimination that occurs in more traditional alkylation reactions between enolates and alkyl electrophiles. DFT studies suggest the intermediacy of copper(II) enolates [CuII](CH2C(O)Ar) that capture alkyl radicals R• to give R-CH2C(O)Ar under competing dimerization of the copper(II) enolate to give the 1,4-diketone ArC(O)CH2CH2C(O)Ar. 

   more » « less
4. Creating, Preserving, and Directing Carboxylate Radicals in Ni-Catalyzed C(sp 3 )–H Acyloxylation of Ethers, Ketones, and Alkanes with Diacyl Peroxides

   https://doi.org/10.1021/acs.organomet.2c00663  

   Vil’, Vera A. ; Barsegyan, Yana A. ; Kuhn, Leah ; Terent’ev, Alexander O. ; Alabugin, Igor V. ( March 2023 , Organometallics)

   The reaction of Ni(II) acetate with diacyl peroxides produces high-valence Ni-species capable of catalytic oxidative acyloxylation of C(sp3)–H bonds in ethers, ketones, and alkanes. The desired esters were obtained in 20–82% yields. Computational analysis suggests that activation of the peroxide moiety produces a dynamically interconverting mixture of catalytic Ni-species in the formal Ni(III) state. Remarkably, in these species, coordination of the RCO2 group at Ni preserves radical character at the carboxylate moiety (i.e., carboxylate radical acts as an “L-ligand”), so the latter can induce fast C–H abstraction. The spirocyclopropyl moiety prevents premature radical decarboxylation via a combination of hybridization factors and stereoelectronic effects. A variety of viable C–H activation patterns were identified experimentally and computationally. 

   more » « less
5. C–H functionalization reactions enabled by hydrogen atom transfer to carbon-centered radicals

   https://doi.org/10.1039/D0SC04881J  

   Sarkar, Sumon ; Cheung, Kelvin Pak ; Gevorgyan, Vladimir ( December 2020 , Chemical Science)

   null (Ed.)

   Selective functionalization of ubiquitous unactivated C–H bonds is a continuous quest for synthetic organic chemists. In addition to transition metal catalysis, which typically operates under a two-electron manifold, a recent renaissance in the radical approach relying on the hydrogen atom transfer (HAT) process has led to tremendous growth in the area. Despite several challenges, protocols proceeding via HAT are highly sought after as they allow for relatively easy activation of inert C–H bonds under mild conditions leading to a broader scope and higher functional group tolerance and sometimes complementary reactivity over methods relying on traditional transition metal catalysis. A number of methods operating via heteroatom-based HAT have been extensively reported over the past few years, while methods employing more challenging carbon analogues have been less explored. Recent developments of mild methodologies for generation of various carbon-centered radical species enabled their utilization in the HAT process, which, in turn, led to the development of remote C(sp 3 )–H functionalization reactions of alcohols, amines, amides and related compounds. This review covers mostly recent advances in C–H functionalization reactions involving the HAT step to carbon-centered radicals. 

   more » « less